Department of Experimental Diabetology (DIAB), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Diabetologia. 2017 Nov;60(11):2274-2284. doi: 10.1007/s00125-017-4389-x. Epub 2017 Aug 2.
AIMS/HYPOTHESIS: Fibroblast growth factor 21 (FGF21) is considered to be a promising therapeutic candidate for the treatment of type 2 diabetes. However, as FGF21 levels are elevated in obese and diabetic conditions we aimed to test if exogenous FGF21 is sufficient to prevent diabetes and beta cell loss in New Zealand obese (NZO) mice, a model for polygenetic obesity and type 2 diabetes.
Male NZO mice were treated with a specific dietary regimen that leads to the onset of diabetes within 1 week. Mice were treated subcutaneously with PBS or FGF21 to assess changes in glucose homeostasis, energy expenditure, food intake and other metabolic endpoints.
FGF21 treatment prevented islet destruction and the onset of hyperglycaemia, and improved glucose clearance. FGF21 increased energy expenditure by inducing browning in subcutaneous white adipose tissue. However, as a result of a compensatory increased food intake, body fat did not decrease in response to FGF21 treatment, but exhibited elevated Glut4 expression.
CONCLUSIONS/INTERPRETATION: FGF21 prevents the onset of diet-induced diabetes, without changing body fat mass. Beneficial effects are mediated via white adipose tissue browning and elevated thermogenesis. Furthermore, these data indicate that obesity does not induce FGF21 resistance in NZO mice.
目的/假设：成纤维细胞生长因子 21（FGF21）被认为是治疗 2 型糖尿病的有前途的治疗候选物。然而，由于肥胖和糖尿病患者的 FGF21 水平升高，我们旨在测试外源性 FGF21 是否足以预防新西兰肥胖（NZO）小鼠的糖尿病和β细胞丢失，NZO 小鼠是多基因肥胖和 2 型糖尿病的模型。
雄性 NZO 小鼠接受特定的饮食方案治疗，该方案在 1 周内导致糖尿病发作。用 PBS 或 FGF21 皮下处理小鼠，以评估葡萄糖稳态、能量消耗、食物摄入和其他代谢终点的变化。
FGF21 治疗可预防胰岛破坏和高血糖的发生，并改善葡萄糖清除率。FGF21 通过诱导皮下白色脂肪组织中的褐色化来增加能量消耗。然而，由于补偿性食物摄入量增加，FGF21 治疗并未导致体脂肪减少，但表现出 Glut4 表达增加。
结论/解释：FGF21 可预防饮食诱导的糖尿病的发生，而不会改变体脂肪量。有益作用是通过白色脂肪组织褐变和提高产热来介导的。此外，这些数据表明肥胖不会诱导 NZO 小鼠产生 FGF21 抵抗。
